Frequency dependant topological alterations of intrinsic functional connectome in major depressive disorder

Abstract

Major depressive disorder is associated with aberrant topological organizations of brain networks. However, whether this aberrance is shown in broader frequency bands or in a specific frequency band remains unknown. Fifty patients and fifty gender, age and education matched normal controls underwent resting state functional magnetic resonance imaging. Frequency dependent topological measures based on graph theory were calculated from wavelet decomposed resting state functional brain signals. In the specific frequency band of 0.03-0.06 Hz, the clustering coefficient and the global efficiency were reduced while the characteristic path length was increased. Furthermore, patients showed aberrant nodal centralities in the default mode network, executive network and occipital network. Network based statistical analysis revealed system-wise topological alterations in these networks. The finding provides the first systematic evidence that depression is associated with frequency specific global and local topological disruptions and highlights the importance of frequency information in investigating major depressive disorders.

Figure 1. Group comparisons of fitted number of connections, fitted mean correlation strength and fitted mean anatomical distance (mean Euclidean distance across existing edges) across four wavelet scales.

* denotes that p < 0.05; # denotes that 0.05 < p < 0.1.

Figure 2. Group comparisons of global topological metrics across four wavelet scales.

Here, only topological metrics which show significant group differences are presented. These metrics include clustering coefficient (upper left), characteristic path length (upper right) and global efficiency (lower left). * denotes that p < 0.05; # denotes that 0.05 < p < 0.1.

Figure 3. Regions which show significant decreased degree centrality (Upper panel, A) and increased betweenness centrality (Lower panel, B) in patients.

CARET software (CARET; http://brainvis.wustl.edu) was used for surface rendering. The cold color represents that the degree centrality of a given region was significantly (p < 0.05, uncorrected) lower in MDD patients. The hot color represents that the betweenness centrality of a given region was significantly (p < 0.05, uncorrected) lower in MDD patients. The color bar indicates p value;

Figure 4. Networks with decreased connections in patients.

(A) The larger network identified by the network based statistical (NBS) analysis method under the liberal primary threshold of p < 0.005; (B) The smaller network identified by NBS under the strict primary threshold of p < 0.001; BraiNet Viewer (http://www.nitrc.org/projects/bnv/) was used for visualization.

Figure 5. Regions showing significant correlations between nodal centrality and HRSD score.

Fitted degree centrality was calculated by regressing out nuisance variables. HRSD: Hamilton Rating Scale for Depression.